6-mercaptopurine (6-MP) metabolite monitoring and TPMT testing in patients with inflammatory bowel disease
- Richard P MacDermott, MD
Richard P MacDermott, MD
- Emeritus Professor of Medicine, Division of Gastroenterology
- The Albany Medical College
The therapeutic efficacy, bone marrow toxicity, and liver toxicity of azathioprine (AZA) and 6-mercaptopurine (6-MP) may be related to their metabolites: 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP). AZA is a prodrug that is metabolized to 6-MP, which is then further metabolized along an anabolic pathway to several metabolites including 6-TG and 6-MMP. Two enzymes are responsible for catalyzing these reactions: thiopurine methyltransferase (TPMT) and hypoxanthine phosphoribosyl transferase (figure 1). 6-TG levels between 230 and 400 may correlate with response and remission of inflammatory bowel disease. Bone marrow suppression may correlate with elevated levels of 6-TG greater than 400, while elevated levels of 6-MMP levels greater than 5700 may correlate with liver toxicity, manifested as increased liver enzymes.
This topic will review 6-MP metabolite monitoring and TPMT testing in patients with inflammatory bowel disease, and the discussion is generally consistent with the American Gastroenterological Association (AGA) guideline on therapeutic drug monitoring in inflammatory bowel disease . The approach to medical management of Crohn disease and ulcerative colitis is discussed separately.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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- TPMT ENZYME DETERMINATION
- TPMT genotyping
- TPMT phenotyping
- Routine laboratory testing
- Therapeutic drug monitoring
- - Following 6-TG levels for optimal dosing of AZA or 6-MP
- - Following 6-TG and 6-MMP levels to predict toxicity AZA or 6-MP
- - Demonstration of AZA/6-MP non-compliance or resistance
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS